16 Drug-drug interactions and adverse drug reactions in neonates

Introduction Due to off-label medications, PK/PD variability, and organ dysfunction/immaturity, the incidence of drug-related problems was higher in neonatal intensive care units (NICUs) compared with other paediatric wards. The aim of this study was to determine the probability (causality) and severity of each adverse drug reaction (ADR) and clinically significant drug-drug interaction (cDDI) with newer agents in neonates during NICU hospitalisation. Methods In this prospective cohort study, each ADR and DDI was assessed using neonatal-specific probability and severity scales. Whether ADRs and DDIs were actually drug-related or not was assessed using the Du's tool for ADRs in neonates and the drug interaction probability scale. The severity of ADRs and DDIs was also determined using the neonatal adverse event severity scale (NAESS) developed by the International Neonatal Consortium and the Lexicomp® drug interaction database. Results During the study period, a total of 109 neonates were screened and 100 neonates fulfilled the inclusion criteria. All ADRs fell into the "definite" category on the Du's tool. According to the NAESS, 34 (41.5%) of all ADRs (n=82) were considered mild, 27 (32.9%) moderate, 17 (20.7%) severe and 4 (4.9%) life-threatening. All cDDIs fell into the "highly probable" category on the drug interaction probability scale. According to the Lexicomp® drug interaction database, 33 (94.4%) of all cDDIs (n=35) were C (monitor therapy is needed), 1 (2.8%) D (consider therapy modification) and 1 (2.8%) B (no action needed). Conclusions The use of specific and up-to-date tools to predict the probability and severity of ADRs and cDDIs with the most accurate methods from admission to discharge in neonates, a highly vulnerable population, greatly contributes to clinician decision-making throughout personalised pharmacotherapy. Well-designed randomised controlled trials with larger populations are needed to determine the probability and severity of ADRs and cDDIs.